congenic mice confirm that collagen x is required for proper hematopoietic development句老鼠证实胶原x是适当的造血所需的发展.pdfVIP

Congenic Mice Confirm That Collagen X Is Required for Proper Hematopoietic Development Elizabeth Sweeney, Douglas Roberts, Tina Corbo, Olena Jacenko* Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Abstract The link between endochondral skeletal development and hematopoiesis in the marrow was established in the collagen X transgenic (Tg) and null (KO) mice. Disrupted function of collagen X, a major hypertrophic cartilage matrix protein, resulted in skeletal and hematopoietic defects in endochondrally derived tissues. Manifestation of the disease phenotype was variable, ranging from perinatal lethality in a subset of mice, to altered lymphopoiesis and impaired immunity in the surviving mice. To exclude contribution of strain specific modifiers to this variable manifestation of the skeleto- hematopoietic phenotype, C57Bl/6 and DBA/2J collagen X congenic lines were established. Comparable disease manifestations confirmed that the skeleto-hematopoietic alterations are an inherent outcome of disrupted collagen X function. Further, colony forming cell assays, complete blood count analysis, serum antibody ELISA, and organ outgrowth studies established altered lymphopoiesis in all collagen X Tg and KO mice and implicated opportunistic infection as a contributor to the severe disease phenotype. These data support a model where endochondral ossification-specific collagen X contributes to the establishment of a hematopoietic niche at the chondro-osseous junction. Citation: Sweeney E, Roberts D, Corbo T, Jacenko O (2010) Congenic Mice Confirm That Collagen X Is Required for Proper Hematopoietic Development. PLoS ONE 5(3): e9518. doi:10.1371/journal.pone.0009518